To improve the accuracy and sensitivity of early diagnosis of diseases, it’s essential to make full use of the strengths of all kinds of imaging modalities. One ideal solution is to combine two or more imaging elements in one platform for dual mode or multimode imaging applications. In addition, nanoparticles (NPs) often suffer quick clearance by reticuloendothelial system (RES) once they are injected to the body. Therefore, it’s critical to render the NPs with good antifouling properties. Herein, we describe the synthesis of three antifouling agents modified generation 5 (G5) polyamidoamine (PAMAM) dendrimers entrapped with gold nanoparticles (Au DENPs). Through protein resistance, macrophage cellular uptake and pharmacokinetics assays, we show that Au DENPs modified with 1,3-propane sultone (1,3-PS) exhibit the best antifouling property. We then prepared G5 PAMAM dendrimer platform modified with Gd (III) chelator DOTA, targeting agent arginine-glycine-aspartic acid (RGD) peptide, 1,3-PS and used them as templates to synthesize Au DENPs, followed by Gd (III) chelation. In particular, the formed multifunctional Au DENPs displayed enhanced X-ray attenuation property, high r<sub>1</sub> relaxivity (13.3 mM s<sup>-1</sup>), good cytocompatiably, targeting specificity, and enabled effective dual mode CT/MR imaging of a lung cancer metastasis model in vivo. The developed multifunctional zwitterion-functionalized Au DENPs may be potentially used as an efficient nanoprobe for enhanced dual-modal CT/MR imaging of other cancer types.

Zwitterion-modified dendrimer-entrapped gold nanoparticles loaded with gadolinium for enhanced CT/MR imaging of lung cancer metastasis

2019 Spring National Meeting

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